The majority of sensorineuronal hearing loss involves the loss of auditory mechanoreceptors called hair cells. Unfortunately, evidence of hair cell regeneration in the postnatal or adult organ of Corti (auditory sensory organ) has never been observed in mammals. We have identified a rather ubiquitous and potent cell cycle inhibitor that when deleted allows the organ of Corti to regenerate some of its hair cells spontaneously. Once more, the organ of Corti of mice containing one copy of the gene and 50% of normal protein levels are capable of auditory hair cell regeneration. Mechanistically, we have the molecular tools to inhibit this protein in wt animals that possess normal copies of the gene. We must determine whether this strategy of "inhibiting a growth inhibitor" can result in renewed supporting cell proliferation, hair cell regeneration and recovery of function in the wt organ of Corti. This methodology may prove useful in stimulating auditory hair cell regeneration as means of regenerating hearing in the hearing impaired. PROPOSED COMMERCIAL APPLICATION: 1. To further develop a therapeutic product for clinical trials that will induce hair cell regeneration and restore hearing in hearing impaired 2. To ultimately sell, sublicense or partrter to produce revenues based on our p27 technology that was exclusively licensed from the FHCRC and SKI.